Elsevier

Blood Reviews

Volume 21, Issue 6, November 2007, Pages 327-348
Blood Reviews

Review
Transfusion-related immunomodulation (TRIM): An update

https://doi.org/10.1016/j.blre.2007.07.003Get rights and content

Summary

Allogeneic blood transfusion (ABT)-related immunomodulation (TRIM) encompasses the laboratory immune aberrations that occur after ABT and their established or purported clinical effects. TRIM is a real biologic phenomenon resulting in at least one established beneficial clinical effect in humans, but the existence of deleterious clinical TRIM effects has not yet been confirmed. Initially, TRIM encompassed effects attributable to ABT by immunomodulatory mechanisms (e.g., cancer recurrence, postoperative infection, or virus activation). More recently, TRIM has also included effects attributable to ABT by pro-inflammatory mechanisms (e.g., multiple-organ failure or mortality). TRIM effects may be mediated by: (1) allogeneic mononuclear cells; (2) white-blood-cell (WBC)-derived soluble mediators; and/or (3) soluble HLA peptides circulating in allogeneic plasma. This review categorizes the available randomized controlled trials based on the inference(s) that they permit about possible mediator(s) of TRIM, and examines the strength of the evidence available for relying on WBC reduction or autologous transfusion to prevent TRIM effects.

Section snippets

History and definition of TRIM

Over 30 years ago, it was reported that pre-transplant ABTs could improve renal-allograft survival in patients who had undergone renal transplantation.9 This beneficial immunosuppressive effect of ABT has been confirmed by animal data, observational clinical studies, and clinical experience worldwide, although it has not been proven in randomized controlled trials (RCTs). Before the advent of the AIDS pandemic, it had become standard policy in many renal units to deliberately expose patients on

Possible mechanisms and mediators of TRIM effects

Although the mechanisms of TRIM have been debated extensively, the exact mechanism(s) of this phenomenon has yet to be elucidated. A number of putative mechanisms have been postulated and are summarized in Table 1.7, 8 The three major mechanisms accounting for much of the experimental data include: clonal deletion, induction of anergy, and immune suppression. Conceptually, clonal deletion refers to the inactivation and removal of alloreactive lymphocytes that would, for example, cause the

Inferences on TRIM mediators permitted by RCTS investigating adverse TRIM effects

Twenty-two RCTs20, 21, 22, 50, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86 have investigated the adverse TRIM effects potentially attributable to WBC-containing ABT. Table 2 categorizes these RCTs based on the type of RBC product transfused to patients in the arm receiving RBC products depleted of allogeneic WBCs and/or allogeneic plasma. Patients assigned randomly to this arm received (pre- or post-storage-filtered) WBC-reduced allogeneic RBCs or whole blood, or

Preclinical and clinical studies of the “pro-inflammatory” effect of ABT

The Canadian before-and-after study of premature infants,97 did not observe a difference in mortality or in the risk of bacteremia between the two study periods (before or after implementation of universal WBC reduction). Instead, the implementation of WBC reduction coincided with a reduction in several secondary morbidity outcomes from several organ systems (i.e., bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis)-an observation that would be consistent with a

Conclusions

The totality of the evidence from RCTs does not demonstrate a TRIM effect manifest across all clinical settings and transfused RBC products. Instead, WBC-containing ABT is associated with an increased risk of short-term (up to 3-month post transfusion) mortality from all causes combined specifically in cardiac surgery. The additional deleterious TRIM effect detected by the latest meta-analysis95 (i.e., the effect on postoperative infection prevented by poststorage filtration) contradicts

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